1. Field of the Invention
The invention mainly relates to a novel microorganism strain, Lactobacillus fermentum GM-090 and its use for stimulating IFN-γ secretion and/or treating allergy.
2. Description of the Related Art
Allergy refers to an acquired potential to develop immunologically mediated adverse reaction to normally innocuous substances. Allergic reaction provokes symptoms such as itching, coughing, wheezing, sneezing, watery eyes, inflammation and fatigue. It is believed that allergic reaction includes an early specific immune response and a late inflammatory reaction. It was reported that allergens (e.g. pollens and mite dust) mediated the early phase of allergy by stimulating high affinity immunoglobulin (IgE) receptors. For instance, mast cells and basophils, when stimulated by allergens, would release histamine and cytokines. The cytokines released from mast cells and basophils then mediated the late phase of allergy by recruiting inflammatory cells (see Serafin, W E, In Goodman and Gillmans, “The Pharmacological Basis of Therapeutics”, Hardmen, Ja; Limbird, L, E eds, McGraw-Hill, N.Y., 659-682, 1996). It was also reported that the influx of eosinophils, macrophages, lymphocytes, neutrophils and platelets started the vicious inflammatory cycle. The late phase of allergy amplified the initial immune response, which in turn triggered the release of more inflammatory cells (Townley, R G and Okada, C, Annals of Allergy, 68: 190-196, 1991).
Various therapies have been pursued in order to treat the symptoms of allergies. Among them, anti-allergics and histamine H-receptor antagonists (anti-histamines) have been used. Histamine antagonists were administered to antagonize the action of histamine released from mast cells in response to the presence of allergens. They reduced the redness, itching and swelling caused by the action of histamine on the target tissues, and served to prevent or alleviate many of the symptoms resulting from degranulation of mast cells. However, anti-histamines were also reported to be associated with adverse reactions such as diminished alertness, slowed reaction times and somnolence (Goodman and Gillman, The Pharmacological Basis of Therapeutics, Eighth Edition, Pergamon Press, New York, pages 575-588, 1990).
There are also some reports on the treatment of allergies by regulating cytokines. Among them, interferon-γ (IFN-γ) was found to inhibit the over-expression of cytokines in Th2 lymphocytes, especially the secretion of IL-4 to lower the proliferation of B cells. Besides, IFN-γ could stimulate the immune response of Th1 and repress the synthesis of IgE (Sareneva T et al., Influenza A virus-induced IFN-α/β and IL-18 synergistically enhance IFN-γ gene expression in human T cells. J Immunol 160:6032-6038, 1998; Shida K et al., Lactobacillus casei inhibits antigen-induced IgE secretion through regulation of cytokine production in murine splenocyte culture. Int Arch Allergy Immunol 115:278-287, 1998). Since IFN-γ can repress B cell proliferation and IgE secretion, it is believed that IFN-γ is effective in treating allergy.
Lactic acid bacteria, which are gram-positive bacteria, are commonly used in industrial food fermentations. In recent studies, lactic acid bacteria were shown to stimulate IFN-γ secretion of cells (Blum S et al., Intensinal microflora and the interaction with immunocompetent cells. Antonie Van Leeuwenhoek 67:199-205, 1999; Contractor NV et al., Lymphoid hyperplasia, autoimmunity and compromised intestinal intraepithelial lymphocyte development in colits-free gnotobiotic IL-2-deficient mice. J Immunol 160:385-394, 1998; Delneste Y et al., Functional foods: Mechanism of action on immuncompetent cells. Nutr Rev 56:593-98, 1998; Haller D et al., Non-pathogenic bacteria elicit a different cytokine response by intestinal epithelial cell/leucocyte co-culture. Gut 47:79-87, 2000). Some specific lactic acid bacteria, such as Bifidobacterium lactis and Lactobacillus brevis subsp., were found to stimulate IFN-γ secretion of lymphocytes in blood derived from mice and humans (Arunachalam K et al., Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN 019). Eur J Clin Nutr 54:1-5, 2000; Kishi A et al., Effect of the oral administration of Lactobacillus brevis subsp. Coagulans on interferon-α producing capacity in humans. J Am Coll Nutr 15:408-412, 1996). It was also reported that lactic acid bacteria could stimulate lymphocytes derived from humans or mice to secret Interleukin-12 (IL-12), which was a T cell stimulatory cytokine activating T cells and NK cells to secrete IFN-γ (Pouwels P H et al., The potential of Lactobacillus as a carrier for oral immunization: development and preliminary characterization of vector systems for targeted delivery of antigens. J Biotechnol 44:183-92, 1996).
A topic dermatitis is one of the most common allergic diseases in children. The conventional method for treating a topic dermatitis is topic steroid therapy. However, the symptoms persist and recur frequently after stopping administrating steroids. Probiotic therapy is regarded as a safer and more effective way to treat a topic dermatitis. Some lactic acid bacteria were suggested to be effective in prevention and/or treatment of a topic dermatitis, such as L. rhamnosus strain GG (Kalliomaki, M., S. Salminen, et al., Probiotics and prevention of a topic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet 361(9372): 1869-71, 2003; Kirjavainen, P. V., S. J. Salminen, et al., Probiotic bacteria in the management of a topic disease: underscoring the importance of viability. J Pediatr Gastroenterol Nutr 36(2): 223-7, 2003; Dreborg, S., The implications of nomenclature. Ann Allergy Asthma Immunol 89(6 Suppl 1): 83-5, 2002; Pessi, T., Y. Sutas, et al., Interleukin-10 generation in a topic children following oral Lactobacillus rhamnosus GG. Clin Exp Allergy 30(12): 1804-8, 2000; Isolauri, E., T. Arvola, et al., Probiotics in the management of a topic eczema. Clin Exp Allergy 30(11): 1604-10, 2000), the combination of L. rhamnosus 19070-2 and L. reuteri DSM 122460 (Rosenfeldt, V., E. Benfeldt, et al., Effect of probiotic Lactobacillus strains in children with a topic dermatitis. J Allergy Clin Immunol 111(2): 389-95, 2003), and Bifidobacterium lactitis Bb-12 (Isolauri, E., T. Arvola, et al., 2000).